ISBN : 974-422-086-4

1 : 2547
: 4,000
:


50
80

(Palliative care)




90

( )

2547



Age-Standardized Incidence Rates (ASR)
.. 2535-2537 151.3
123.8 ..
2538-2540 149.2 125.0
.. 2536 32,801 30,940 35,539
38,467 .. 2539 (Cancer in Thailand Vol. III, 1995-1997)
.. 2542
36,091 .. 2543 39,480 .. 2546
47,200
80
60-90 70

90




18

13
6



Adjuvants

( )

2547

....................................................................................................................
..........................................................................................................
........................................................................................................
........................................................................
............................................................................
............................................................................................
..................................................................................................
.............................................................................................
Nociceptive pain ......................................................
Neuropathic pain .....................................................
..............................................................................
Opioids ....................................................
Opioids...........................................................
NSAIDs paracetamol..........................................................................
NSAIDs ................................................................................
NSAIDs .....................................................
........................................................................................................
.......................................................................
................................
........................................................
...........................................................
.............................................................................................................
Brief Pain Inventory....................................................................................
.........................................................................................................
...........................................................................................................

1
2
2
2
4
6
13
14
15
15
16
16
21
24
26
26
27
29
29
31
31
34
34
38
40

1 Nociceptive Neuropathic pain.............

2 18
3 Equianalgesic Doses for Converting Morphine to
Transdermal Fentanyl .......................................................................

20

4 NSAIDs
.......................................................................... 25
5 Adjuvants Coanalgesics ............................................. 28-29
6 opioids 37

1
...........................................

2 ....................................

10

3 .....................................

11

4 ..................................

12

5 ........................................................ 32-33

.. 2542 .. 2546 .. 2544
68.4 .. 2545 73.3
(Cancer in Thailand Vol. III, 1995-1997) .. 2533
57,968 .. 2539 74,000


(Palliative Care)

90 (United
States Department of Health and Human Services, 1994)
(WHO, 1998 b)


1. /
2.
3.

.
1. 78



vasospasm, venous
thrombosis, tumor emboli lymphangitis

2. 19





(mucositis)

 steroid (steroid pseudorheumatism)

steroid femur humerus


brachial plexus lumbosacral plexus

(post radiation myelopathy)

3. 3
migraine, tension headache
.




6 Shock, Denial, Anger, Bargain, Depression
Acceptance
( 1)
antidepressants
(psychotherapy)

Shock
Shock
Acceptance
Acceptance

Denial
Denial

Depression
Depression

Anger
Anger

Bargain
Bargain

1. 2
1.1 Nociceptive pain
Nociceptive pain
1.1.1 Somatic pain

mucositis
1.1.2 Visceral pain
somatic visceral pain
referred pain
1.2 Neuropathic Neurogenic pain

neuropathic pain


neuritis
plexopathy
post-surgical syndrome (post-mastectomy, post-amputation )
postherpetic neuralgia

2. 2
(acute pain) (chronic pain) acute chronic pain
acute pain
chronic pain
chronic pain

2.1 (acute pain)
2.1.1 Acute cancer - related pain


(pathological fracture)
2.1.2 Acute pain associated with cancer therapy


(radiation dermatitis),

2.2 (chronic pain)
2.2.1 Chronic pain caused by cancer progression
90

2.2.2 Chronic pain associated with cancer therapy
neuropathic pain

2.2.3 Pre - existing chronic pain and cancer - related pain
( trigeminal
neuralgia)
2.2.4 Drug addiction and cancer - related pain


2.2.5 Dying patient with pain

 (Pain Assessment)

(sensory domain) (affective
domain) (cognitive - evaluative domain)



1.
1.1
1.1.1


Numerical rating scale (NRS) Verbal rating scale (VRS)
? 0 10

0

9 10

Visual analog scale (VAS) 10 ..

Categorical scale Verbal descriptive scale

?

1-3

4-6

7-10

Wong - Baker faces pain rating scale

3 numerical rating scale

10

1.1.2 Body chart

( )
1.1.3 3
Somatic pain (aching)
(stabbing) (throbbing) (pressure)
Visceral pain (cramping)
(gnawing) (sharp)
Neuropathic pain
(burning) (electrical, shooting) (tingling)
(pins and needles) (radiating pain
radicular pain) (allodynia)
(periodic)
neuropathic pain nociceptive pain

 1 Nociceptive Neuropathic pain

Nociceptive pain (somatic and visceral)

constant and well localized

vague in distribution and quality
aching, throbbing, gnawing,
deep dull aching, dragging, squeezing,
pressure - like

*
**
***
****
*****

Neuropathic pain

may be constant, steady, and

spontaneously maintained, intermittent
shock-like, shooting, lancinating,
electrical, burning, tingling, numbing,
pressing, squeezing, itching, dysesthesia*,
hyperalgesia**, allodynia***,
hyperesthesia****, hyperpathia*****

Dysesthesia
Hyperalgesia
Allodynia
Hyperesthesia
Hyperpathia

1.1.4





breakthrough pain
incident pain breakthrough pain
incident pain (prn)
1.1.5



1.2
1.2.1
1.2.2
1.2.3
1.2.4

1.3
1.3.1
1.3.2
1.3.3
1.3.4

1.4

neuropathic pain

2.

pain behavior





3.


3
3.1
3.2
electrodiagnostic neurophysiologic test
3.3 hematologic, biochemical,
metabolic endocrine blood chemistries

Universal
screening
Universal screening

(VAS1-3)
1-3)
(VAS

(VAS
(VAS4-6)
4-6)

(VAS
(VAS7-10)
7-10)

Nociceptive
Nociceptive
Neuropathic
Nouropathic
Somatic
Somatic
Visceral
Visceral
Refered
Refered

2


(breakthrough pain) prn

WHO Analgesic Ladder

nociceptive neuropathic pain

10

1-3
1-3

paracetamol NSAIDs
opioids
/

24-72
24-72

4-6

4-6

/ opioids*

24-48
24-48

7-10

7-10
/
opioids

2424

* opioids immediate release form

morphine

3 WHO Analgesic
Ladder

11

P6P6

P3

P 3

-
-

-- Coanalgesic
Coanalgesic
- Cognitive & behavioral modalities
- Cognitive & behavioral modalities

PP22
P14
P14

Nerve
Nerve blocks

Coanalgesic
Coanalgesic

P16

P16

NSAIDs
NSAIDs
opioids
opioids
Bisphosphonates
Bisphosphonates

Nerveblock
block
Nerve

Neuropathic
pain
Neuropathc pain
Antidepressant/Anticonvulsant

Nerve block

Nerve stimulation
Neurolytic procedures

Nerve block
Neuroablative surgery
Neurolytic

Mucositis

Mucositis

Opioids
Opioids

TransdermalIVIV
Transdermal

Corticosteroids
Corticosteroids

P =

12








1.
2.
WHO Analgesic Ladder ( 1)
3.

breakthrough pain
4.
5. Co-analgesic
5.1 Antidepressant : amitriptyline, nortriptyline
5.2 Antianxiety : lorazepam
5.3 Anticonvulsant : carbamazepine, gabapentin, oxcarbazepine
6.
opioids non-opioids corticosteroids opioids

7.
8. Neuropathic pain tricyclic antidepressants anticonvulsants
opioids non-opioids opioids
neuropathic pain
9.



10.

11.

12.
13. /

13

Pain
Pain
persisting
persisting
ororincreasing
increasing

SEVERE
PAIN
SEVERE
PAIN
MODERATE PAIN
MODERATE
PAIN

MILD PAIN
MILD
PAIN
Non-opioids
Non-opioid
Adjuvants*
+ Adjuvant*
Paracetamol
Paracetamol
Aspirin
Aspirin
NSAIDs
NSAIDs

Weak
opioids
Weak opioid
+Non-opioids
Non-opioid
+Adjuvants*
Adjuvant*
Codeine
Codeine
Tramadol
Tramadol

Strong
opioids
Strong opioid
+ Non-opioids
Non-opioid
+ Adjuvants*
Adjuvant*
Morphine
Morphine
Fentanyl
Fentanyl
Methadone
Methadone

* 28-29

1 WHO Analgesic Ladder

1. 3 (WHO Analgesic Ladder)

1 non-opioids paracetamol, aspirin

NSAIDs
2 weak opioids codeine
tramadol
3 weak opioids
strong opioids morphine, fentanyl methadone
2. 1 2 3
weak opioids strong opioids
3. NSAIDs nociceptive pain
conventional NSAIDs

H2 blockers, misoprostol, omeprazole selective COX-2 inhibitors coxibs

14

4. opioids

5. Coanalgesics Adjuvants
5.1 Antidepressants amitriptyline, imipramine, desipramine
nortriptyline

5.2 Anticonvulsants carbamazepine, oxcarbazepine, phenytoin,

sodium valproate gabapentin
5.3 Steroids

6.

Nociceptive pain
1. (WHO)
2.

Neuropathic pain
1. Primary shooting pain (radiating)
3-5
carbamazepine, gabapentin,
oxcarbazepine phenytoin
2. Primary burning pain
touch allodynia
dysesthesia (paresthesia)
Antidepressants
3-5

amitriptyline, nortriptyline, doxepin, desipramine venlafaxine
3. Topical agents (topical agents)
(lidocaine jelly / cream / EMLA) capsaicin cream ()

15

4. 2-3

invasive procedure

(bone pain)
1. NSAIDs / opioids
2. 2-3
nerve blocks
3.
3.1 bisphosphonates pamidronate, alendronate, zoledronic acid, disodium
clodronate multiple myeloma
/

3.2 systemic anticancer antiandrogen (flutamide), antiestrogen (tamoxifen)

3.3 Calcitonin Miacalcic
osteoclast
3.4
radioactive substance Strontium89, Samarium153 glucocorticoids
/ radioisotopes131
3.5
4.

4.1 Invasive anesthetic technique nerve blocks
opioids epidural space
4.2

opioids

1.

16

2.


opioids
( NSAIDs ) weak opioids codeine
tramadol

opioids strong
opioids morphine immediate release 5-10
4

weak opioids strong opioids
weak opioids strong opioids 1
equianalgesic dose morphine fentanyl 2
3 25
3. opioids opioids
immediate release (around the clock)
breakthrough pain incident pain opioids immediate release
25-50 regular dose ( 4-6 ) prn
4. (codeine 15-30 4 , tramadol
50-100 6-8 morphine 5-10 4 )

(pain score 4-6)
25-50
(pain score 7-10)
50-100
5. opioids immediate release
opioids ( around the clock prn) 24
opioids sustained release

6. sustained release morphine rescue

analgesic breakthrough pain immediate release
morphine incident pain rescue analgesic rescue analgesic 1/8-1/6
4
1 rescue analgesic
3 regular dose

17

7. codeine paracetamol tramadol

paracetamol
paracetamol paracetamol 4 /
8.
25
2

Equianalgesic dose
(mg)
Parenteral

Morphine 10 (IM, IV, SC)

Methadone
Codeine
Tramadol
100

half-life Analgesic onset Analgesic duration*

(oral)
(h)
(min)
(h)
Oral

30
20
240
100

2
15-30
2-3
6-7

10-20
10-20
10-20
< 60

3-5
4-8
4-6
4-6

* analgesic duration sustained release morphine immediate release

9. Opioids cancer pain chronic noncancer pain

9.1 Pethidine (meperidine) half-life toxic metabolite norpethidine
renal insufficiency pethidine norpethidine

9.2 mixed agonist-antagonists

nalbuphine
ceiling effect
pentazocine
ceiling effect
pentazocine sigma receptor agonist dysphoria confusion
9.3 partial agonist buprenorphine
ceiling effect mixed agonist-antagonist
opioids maintenance therapy
1. opioids sustained release chronic persistent pain
opioids immediate release 24
opioids sustained released ( 1 2547)

18

1.1 MST 10, 30, 60 onset 1-11/2

12
sustained release MST
MST
8-9 10 MST 8-10

1.2 Kapanol 20, 50, 100 onset 2-4
24
1.3 Durogesic (Fentanyl TTS) 2.5, 5.0 10
25, 50 100 /
17-24 opioids
24 48-72
2. opioids sustained release MST
10 2 8.00 . 20.00 . order b.i.d.

3. rescue dose opioids ( immediate release) breakthrough

pain incident pain
3.1 opioids immediate release sustained release
rescue opioids MST Kapanol morphine oral solution morphine
injection oral transmucosal fentanyl citrate
rescue dose Durogesic morphine oral solution morphine
injection rescue opioid
3.2 rescue dose 25-50 regular dose ( 4-6
) prn
4. sustained release rescue dose
3 sustained release

19

 3 Equianalgesic Doses for Converting Morphine to Transdermal Fentanyl

Oral 24 hour
Morphine (mg/day)

IM 24 hour
Morphine (mg/day)

Transdermal
Fentanyl (mg/h)

45-134
135-224
225-314
315-404
405-494
495-584
585-674
675-764
765-854
855-944
945-1034
1035-1124

8-22
23-37
38-52
53-67
68-82
83-97
98-112
113-127
128-142
143-157
158-172
173-187

25
50
75
100
125
150
175
200
225
250
275
300

ratio IM morphine : oral morphine = 1 : 6 morphine

fentanyl TTS morphine

Equianalgesic dose
1 .
oral morphine tablet 30 12 oral morphine solution 15
breakthrough pain
48 morphine
Equianalgesic dose ( 2)
1. oral morphine tablet 24 .
morphine 30 2 dose/
=
60 mg
+ oral morphine solution
=
15 mg

=
75 mg

20

2. . morphine = 75 mg/24
morphine equianalgesic dose 2
2 morphine 30 mg PO
= morphine 10 mg IM/IV
\ morphine 75 mg PO
= morphine 25 mg IM/IV
morphine 4 ( ~ 6 ) .
morphine 25 mg 6 4 mg 4 rescue analgesic
breakthrough pain morphine 1-2 mg
2 . nasopharynx morphine IM 10 mg 4
. fentanyl transdermal

Equianalgesic dose ( 3)
1. IM morphine 24 .
=
60 mg
morphine IM 10 mg 6 dose/
2. morphine 60 mg/day ( 53-67 mg/day) IM equivalent fentanyl transdermal patch 100 g/h
fentanyl transdermal patch onset of action
immediate release morphine 12
transdermal fentanyl TTS
50 g/h ( 3)

Opioids
opioids opiate receptors (,
)
opioids opiate receptors
opioids
1. Sedation Sedation score
0 = none
1 = mild, occasionally drowsy, easy to rouse
2 = moderate, constantly or frequently drowsy, easy to rouse
3 = severe, somnolent, difficult to rouse
S = normal asleep

21

 Sedation
1. opioids

2. opioids 25-50
sedation opioids
1-2 sedation opioids
1-2
sedation
, sedation, sepsis,
electrolyte imbalance, (dehydration)
NSAIDs / co-analgesics anti-depressant,
opioids opioids
opioids


opioids morphine fentanyl

sedation score = 3 10 /
opioids
1. oxygen
2. naloxone titrate dose 0.1
5-10 naloxone
1 naloxone 1
3.
2. m receptors
peristalsis
opioids
opioids

1. fluid intake 2-2.5
,
2.
3.
4. stimulant laxatives bisacodyl, sennoside
stool softeners docusate
bulk forming methylcellulose GI obstruction

22




senna docusate 4
2
coanalgesic opioids
(coanalgesics tricyclic antidepressants amitriptyline )
fecal impaction evacuation


- magnesium hydroxide (MOM) 30-60 ( magnesium
hydroxide )
- bisacodyl 2-3 1
- lactulose 30-60
- sorbitol 30 2 3 prn
1 1
fleet saline water enema
prokinetic agent metoclopramide 10-20 4
3. receptors, chemoreceptor trigger zone (CTZ)
opioids 2
opioids opioids

1.

2.
ondansetron 8 3 IV
8 IV granisetron 2
haloperidol 0.5-1.0 6-8

metoclopromide 5-10 IV, IM 6 10
6
domperidone 10-20 6
(prn)
extrapyramidal side effect haloperidol
metoclopramide
3. 1

opioids

23

coanalgesics

opioids
5-HT3 antagonist ondansetron
8 3 granisetron 2
4. opioids
opioids
intrathecal epidural route

4. Delirium opioids cognitive failure

1. delirium , CNS metastases,
anticholinergic effects
2. opioids
3. coanalgesics opioids
4. haloperidol 0.5-2 4-6
neuroleptic drugs extrapyramidal side effects

5. sedatives
tranquilizers
5. Myoclonus opioids
morphine myoclonus
morphine metabolite myoclonus myoclonus
baclofen, diazepam, clonazepam, midazolam sodium valproate
opioids
6.

NSAIDs paracetamol
NSAIDs paracetamol NSAIDs

NSAIDs ()
ibuprofen

24

 Non-opioid analgesics
paracetamol
500 4 1 6
4
30-60 paracetamol 8
(Extended release) codeine tramadol
NSAIDs NSAIDs
4
4 NSAIDs

()
() ()

Classical NSAIDs
Aspirin
Ibuprofen
Naproxen sodium

300-600
200-400
275

4-6
6-8
12

3600
1600
1100

Indomethacin

50-100

6-12

200

Diclofenac potassium
Piroxicam
Tenoxicam

25-50
10-20
10-20

8
24
24

150
20
20

Selective COX-2 inhibitor

7.5-15
Meloxicam
100-200
Nimesulide

24
12

15
400

Specific COX-2 inhibitor

Celecoxib
Valdecoxib
Etoricoxib

12
24
24

100-200
20-40
60-120

- sustained
release 500 .
-

400
-

25

 NSAIDs
1. 60 ,
compromised fluid states, interstitial nephritis, papillary necrosis, NSAIDs
( cyclosporin, cisplatin, aminoglycosides,
amphotericin B )
2.
60 , ,
major organ dysfunction, NSAIDs , NSAIDs
corticosteroids
3.
aspirin, ibuprofen
4. (photosensitive)
coxibs indomethacin
NSAIDs
, BUN, creatinine, CBC platelet count

NSAIDs
1. NSAIDs BUN creatinine
2
2. NSAIDs
selective COX-2 inhibitor Coxibs
3. NSAIDs
H2 receptor antagonist ( ranitidine, famotidine), Proton pump inhibitors ( omeprazole,
lansoprazole) classical NSAIDs 60
NSAIDs NSAIDs 2
1-2 glucocorticoids
NSAIDs
NSAIDs

26

 (Coanalgesics)
neuropathic pain

Antidepressants tricyclic antidepressants amitriptyline,
imipramine, desipramine, doxepin nortriptyline neuropathic pain


Anticonvulsants carbamazepine, oxcarbazepine, phenytoin, sodium valproate,
clonazepam, gabapentin lamotrigine sharp, shooting
lancinating sensation neuropathic pain
Steroids malignant spinal cord compression, intracranial
pressure , severe bone pain, soft tissue swelling infiltration dexamethasone prednisolone
neuropathic pain antiarrythmic drugs
(lidocaine mexiletine ), baclofen, clonidine, calcitonin
topical capsaicin
bone pain bisphosphonates, calcitonin, radiopharmaceuticals (Strontium 95),
muscle relaxants orphenadrine, methocarbamol
colicky scopolamine sedative tranquillizers

27

 5 Adjuvants Coanalgesics

()

Anticonvulsants
Gabapentin
Phenytoin
Carbamazepine
Oxcarbazepine
Clonazepam

300-3600
300-500
200-1600
300-2400
1-8

PO
PO
PO
PO
PO

Neuropathic pain,
particularly lancinating
or paroxysmal pain

Antidepressants
Amitriptyline
Nortriptyline
Imipramine
Desipramine
Trazadone

10-150
10-100
20-100
25-300
50-225

PO
PO
PO
PO
PO

Neuropathic pain

Corticosteroids
Dexamethasone
Prednisolone

16-90
40-100

PO or IV
PO

Tumor invasion of neural

tissue, elevated intracranial
pressure, spinal cord
compression, additional
effects (mood elevation,
antiemetics, appetite
stimulation)

Antihistamines
Hydroxyzine

75-450

PO or IM

Coanalgesic, antiemetic

Muscle relaxants
Orphenadrine
Toperizone
Methocarbamol
Chlorzoxazone

75-200
50
4000-6000
1500-3000

PO
PO
PO
PO

Occasionally useful for

musculoskeletal pain

28

 5 Adjuvants Coanalgesics ()

Other drugs for neuropathic pain

Baclofen
Clonidine
Capsaicin

()

20-120
0.1-0.6
-

PO
PO
-

Neuropathic pain

Anticholinergics
Hyoscine

2-6

PO

Visceral pain due to

partial bowel obstruction

Psychostimulants
Caffeine
Methylphenidate

50-1000
10-15

PO
PO

Decrease sedation
resulting from opioids

Pain Diary

Brief Pain Inventory (BPI) ()

29


1.

2.

3.

4.

5.

6.

opioids
7.

8.

30

31

/
/

/ /
/
/

opioids

opioids

opioids
opioids

just
justsay
sayno
no

opioids
opioids

ReRe
:
/

:
/

()

5 (I)

32

opioids
opioids

(
(
, , , ,neuropathic)
neuropathic)

/
/

pain
painscale
scale

,
, ,,

== +

5 (II)

33


Brief Pain Inventory (BPI)
1)

?
1.
2.
2) Body chart
(x)

3)
24
0 1 2 3 4 5 6 7 8 9 10
4)
24
0 1 2 3 4 5 6 7 8 9 10
5)
0 1 2 3 4 5 6 7 8 9 10
6)
0 1 2 3 4 5 6 7 8 9 10

34

7)

(Indication)

(Dose)

(Route)

//

8) 24

0 1 2 3 4 5 6 7 8 9 10

9) 24

A.
0 1 2 3 4 5 6 7 8 9 10

B.
0 1

2 3

4 5 6

7 8

9 10

C.
0 1 2 3 4 5 6

7 8

9 10

D. ( )
0 1 2 3 4 5 6 7 8 9 10

E.
0 1 2 3

4 5 6

7 8

9 10

F.
0 1

4 5 6

7 8

9 10

2 3

35

G.
0 1 2 3 4

5 6 7

8 9

10)
A.
0 1 2 3 4 5 6 7 8 9

B. /
0 1 2

10

10

3 4

5 6 7

8 9

10

3 4

5 6 7

8 9

10

C.
0

36

1 2

 6 opioids (

)
Strength
Weak
Codeine
Dextropropoxyphene
Tramadol
Strong
Buprenorphine
Butorphanol
Diamorphine (heroin)
Fentanyl
Hydromorphone
Levophanol
Methadone
Morphine
Nalbuphine
Naloxone
Oxycodone
Pentazocine
Pethidine

Derivatives
Natural alkaloid
Codeine
Morphine
Semisynthetic
Buprenorphine
Diamorphine
Dihydrocodeine
Hydromorphone
Oxycodone
Synthetic
Butorphanol
Dextromoramide
Dextropropoxyphene
Fentanyl
Levorphanol
Methadone
Nalbuphine
Pentazocine
Pethidine
Tramadol

Action
Agonist
Codeine
Diamorphine
Dextromoramide
Dextropropoxyphene
Dihydrocodeine
Fentanyl
Hydromorphine
Levorphanol
Methadone
Morphine
Oxycodone
Pethidine
Tramadol
Partial agonist
Buprenorphine
Mixed agonist-antagonist
Butorphanol
Nalbuphine
Pentazocine
Antagonist
Naloxone
Naltrexone

37


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2. Bonica JJ. Cancer pain. In : Bonica JJ, ed. The Management of pain, 2nd ed. Philadelphia:
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